scholarly journals Obesity-Induced TNFα and IL-6 Signaling: The Missing Link between Obesity and Inflammation—Driven Liver and Colorectal Cancers

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 24 ◽  
Author(s):  
Lara Kern ◽  
Melanie Mittenbühler ◽  
Anna Vesting ◽  
Anna Ostermann ◽  
Claudia Wunderlich ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Insulin Action ◽  
Immune Cell ◽  
Colorectal Cancers ◽  
Low Grade ◽  
Current State ◽  
Immune Cell Subsets ◽  
Factor Α ◽  
Low Grade Inflammation ◽  
Necrosis Factor

Obesity promotes the development of numerous cancers, such as liver and colorectal cancers, which is at least partly due to obesity-induced, chronic, low-grade inflammation. In particular, the recruitment and activation of immune cell subsets in the white adipose tissue systemically increase proinflammatory cytokines, such as tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). These proinflammatory cytokines not only impair insulin action in metabolic tissues, but also favor cancer development. Here, we review the current state of knowledge on how obesity affects inflammatory TNFα and IL-6 signaling in hepatocellular carcinoma and colorectal cancers.

Effect of Etanercept on Insulin Sensitivity in Nine Patients with Psoriasis

2007 ◽  
Vol 20 (4) ◽  
pp. 731-736 ◽  
Author(s):  
M. Marra ◽  
A. Campanati ◽  
R. Testa ◽  
C. Sirolla ◽  
A.R. Bonfigli ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Plasma Levels ◽  
Low Grade ◽  
Model Assessment ◽  
Plaque Type ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Factor Α ◽  
Low Grade Inflammation ◽  
Necrosis Factor

Metabolic syndrome is associated to chronic low grade inflammation, characterized by increased levels of inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6). In particular, TNF-α causes a decrease in the insulin-stimulated kinases related to the early phases of the insulin cascade, thereby leading to insulin resistance. Etanercept is a human fusion protein used in the treatment of psoriasis and inflammatory arthritis. It blocks inflammatory response by interfering in the binding of TNF-α to its receptors. The aim of this case report study is to verify the effect of Etanercept on insulin sensitivity, lipid profile and inflammatory status in psoriatic patients. Nine psoriatic patients with stable, active, plaque type psoriasis were enrolled and treated with Etanercept for 24 weeks. We found an improvement in the metabolic assessment with a significant reduction of insulin plasma levels. In particular, this treatment allows to maintain their euglycemic state with lower insulin plasma levels, as confirmed by the improved Homeostasis Model Assessment (HOMA) index. We conclude that Etanercept, probably acting on inflammation, improves insulin sensitivity in psoriatic subjects.

scholarly journals Tumor necrosis factor-α, kidney function, and hypertension

2017 ◽  
Vol 313 (4) ◽  
pp. F1005-F1008 ◽  
Author(s):  
Eamonn Mehaffey ◽  
Dewan S. A. Majid
Keyword(s):  
Tumor Necrosis Factor ◽  
Proinflammatory Cytokines ◽  
Renal Injury ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Low Grade ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Hypertension is considered to be a low-grade inflammatory condition characterized by the presence of various proinflammatory cytokines. Tumor necrosis factor-α (TNF-α) is a constituent of the proinflammatory cytokines that is associated with salt-sensitive hypertension (SSH) and related renal injury. Elevated angiotensin II (ANG II) and other factors such as oxidative stress conditions promote TNF-α formation. Many recent studies have provided evidence that TNF-α exerts a direct renal action by regulating hemodynamic and excretory function in the kidney. The cytokine incites a strong natriuretic response and plays a part in regulation of the intrarenal renin-angiotensin system. The exact mechanistic role of TNF-α in the development of SSH is as yet poorly understood. While TNF-α antagonism has been shown to attenuate hypertensive responses in many hypertensive animal models, contrasting findings demonstrate that the direct systemic administration of TNF-α usually induces hypotensive as well as natriuretic responses, indicating a counterregulatory role of TNF-α in SSH. Differential activities of two cell surface receptors of TNF-α (receptor type 1 and type 2) may explain the contradictory functions of TNF-α in the setting of hypertension. This short review will evaluate ongoing research studies that investigate the action of TNF-α within the kidney and its role as an influential pathophysiological variable in the development of SSH and renal injury. This information may help to develop specific TNF-α receptor targeting as an effective treatment strategy in this clinical condition.

scholarly journals Comparative Study of Anti-Gouty Arthritis Effects of Sam-Myo-Whan according to Extraction Solvents

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 278
Author(s):  
Yun Mi Lee ◽  
Eunjung Son ◽  
Dong-Seon Kim
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Proinflammatory Cytokines ◽  
High Performance ◽  
Weight Bearing ◽  
Gouty Arthritis ◽  
Extraction Solvents ◽  
Main Components ◽  
Factor Α ◽  
Necrosis Factor

Sam-Myo-Whan (SMW) has been used in Korean and Chinese traditional medicine to help treat gout, by reducing swelling and inflammation and relieving pain. This study compared the effects of SMW extracted by using different solvents, water (SMWW) and 30% EtOH (SMWE), in the treatment of gouty arthritis. To this end, we analyzed the main components of SMWW and SMWE, using high-performance liquid chromatography (HPLC). Anti-hyperuricemic activity was evaluated by measuring serum uric acid levels in hyperuricemic rats. The effects of SMWW and SMWE on swelling, pain, and inflammation in gouty arthritis were investigated by measuring affected limb swelling and weight-bearing, as well as by enzyme-linked immunosorbent assays, to assess the levels of proinflammatory cytokines and myeloperoxidase (MPO). In potassium oxonate (PO)-induced hyperuricemic rats, SMWW and SMWE both significantly decreased serum uric acid to similar levels. In monosodium urate (MSU)-induced gouty arthritis mice, SMWE more efficiently decreased paw swelling and attenuated joint pain compare to SMWW. Moreover, SMWE and SMWW suppressed the level of inflammation by downregulating proinflammatory cytokines (interleukin-1β, tumor necrosis factor-α, and interleukin-6) and MPO activity. HPLC analysis further revealed that berberine represented one of the major active ingredients demonstrating the greatest change in concentration between SMWW and SMWE. Our data demonstrate that SMWE retains a more effective therapeutic concentration compared to SMWW, in a mouse model of gouty arthritis.

Hepatic macrophage accumulation with aging: cause for concern?

2021 ◽  
Author(s):  
Steven A. Bloomer ◽  
Eric Moyer
Keyword(s):  
Healthy Aging ◽  
Intercellular Adhesion Molecule ◽  
Low Grade ◽  
Intercellular Adhesion Molecule 1 ◽  
Age Related ◽  
Hepatic Macrophages ◽  
Liver Macrophage ◽  
Factor Α ◽  
Low Grade Inflammation ◽  
Hepatic Macrophage

Aging is associated with chronic, low-grade inflammation that adversely affects physiological function. The liver regulates systemic inflammation; it is a source of cytokine production and also scavenges bacteria from the portal circulation to prevent infection of other organs. The cells with primary roles in these functions, hepatic macrophages, become more numerous in the liver with "normal" aging (i.e. in the absence of disease). Here we demonstrate evidence and potential mechanisms for this phenomenon, which include augmented tumor necrosis factor-α (TNFα) and intercellular adhesion molecule-1 (ICAM-1) expression in the liver. Also, we discuss how an age-related impairment in autophagy within macrophages leads to a pro-oxidative state and ensuing production of pro-inflammatory cytokines, particularly interleukin 6 (IL-6). Given that the liver is a rich source of macrophages, we posit that it represents a major source of the elevated systemic IL-6 observed with aging, which is associated with physiological dysfunction. Testing a causal role for liver macrophage production of IL-6 during aging remains a challenge, yet interventions that have targeted macrophages and/or IL-6 have demonstrated promise in treating age-related diseases. These studies have demonstrated an age-related, deleterious reprogramming of macrophage function, which worsens pathology. Therefore, hepatic macrophage accrual is indeed a cause for concern, and therapies that attenuate the aged phenotype of macrophages will likely prove useful in promoting healthy aging.

scholarly journals Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice

2019 ◽  
Vol 44 (5) ◽  
pp. 512-520 ◽  
Author(s):  
Débora Romualdo Lacerda ◽  
Michele Macedo Moraes ◽  
Albená Nunes-Silva ◽  
Kátia Anunciação Costa ◽  
Débora Fernandes Rodrigues ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Aerobic Training ◽  
Immune Cell ◽  
Control Diet ◽  
Moderate Intensity ◽  
Low Grade ◽  
Carbohydrate Diet ◽  
Cytokine Levels ◽  
Low Grade Inflammation

Obesity is associated with an energy imbalance that results from excessive energy intake, low diet quality, and a sedentary lifestyle. The increased consumption of a high-refined carbohydrate (HC) diet is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known nonpharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by an HC diet should be further investigated. Our hypothesis herein was that aerobic training would decrease the recruitment of leukocytes in adipose tissue, thereby reducing the levels of cytokines and improving metabolism in mice fed an HC diet. Male Balb/c mice were assigned to the following groups: control diet/nontrained (C-NT), control diet/trained (C-T), high-refined carbohydrate diet/nontrained (HC-NT), and high-refined carbohydrate diet/trained (HC-T). Mice were submitted to moderate-intensity training sessions that consisted of running 60 min per day for 8 weeks. An intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, relative to HC-NT mice, HC-T mice showed increased resting energy expenditure, decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition. Collectively, our data enhance understanding about the anti-inflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.

Chloroquine inhibits proinflammatory cytokine release into human whole blood

1998 ◽  
Vol 274 (4) ◽  
pp. R1058-R1064 ◽  
Author(s):  
Ina Karres ◽  
Jean-Pierre Kremer ◽  
Ingrid Dietl ◽  
Ursula Steckholzer ◽  
Marianne Jochum ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Whole Blood ◽  
Inhibitory Effect ◽  
Potential Effect ◽  
Therapeutic Benefit ◽  
Human Whole Blood ◽  
Weak Bases ◽  
Factor Α ◽  
Dose Dependent ◽  
Necrosis Factor

Excessive synthesis and release of proinflammatory cytokines during endotoxemia causes severe pathophysiological derangements and organ failure. Because the lysosomotropic agent chloroquine has been effective in the treatment of diseases associated with increased secretion of proinflammatory cytokines such as malaria or rheumatoid arthritis, this study evaluates the potential effect of chloroquine on endotoxin-induced cytokinemia using human whole blood from healthy volunteers. Chloroquine revealed a dose-dependent inhibitory effect on endotoxin-induced secretion of tumor necrosis factor-α, interleukin-1β, and interleukin-6 that was associated with reduced cytokine mRNA expression. Moreover, ammonia and methylamine, which react as weak bases like chloroquine, reduced synthesis and secretion of proinflammatory cytokines. These data indicate a potent anti-inflammatory effect of chloroquine on endotoxin-induced synthesis of proinflammatory cytokines that may be due to its weak base effect. Thus chloroquine may be of therapeutic benefit not only during chronic inflammation but also in diseases that are related to bacteria-induced inflammation.

Effects of Isolated Limb Perfusion With Tumor Necrosis Factor-α on Circulating Levels of Proinflammatory Cytokines

2001 ◽  
Vol 24 (4) ◽  
pp. 354-362 ◽  
Author(s):  
Patrizia Ferroni ◽  
Franco Di Filippo ◽  
Francesca Martini ◽  
Antonella Spila ◽  
Roberta D'Alessandro ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Proinflammatory Cytokines ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Isolated Limb Perfusion ◽  
Limb Perfusion ◽  
Factor Α ◽  
Circulating Levels ◽  
Necrosis Factor
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